Differential effect of neocuproine, a copper(I) chelator, on contractile activity in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus

Abstract

The study was conducted to examine effects of a selective copper(I) chelator, neocuproine on the spontaneous or oxytocin-induced contractions in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. Uterus activity was evaluated in tissues obtained from bilaterally ovariectomized non-pregnant rats on the 21st day of the operation ( n = 24), pregnant rats on the 19–21st day of gestation ( n = 24) and women undergoing caesarean section at 38–42 weeks of pregnancy ( n = 15). Neocuproine (100 μM) significantly suppressed the amplitude and frequency of the spontaneous contractions in the ovariectomized non-pregnant rat uterus while this agent facilitated the frequency of the spontaneous or oxytocin-induced contractions in the pregnant rat and human uterus without altering the amplitude of these contractions. At high concentration of 200 μM, neocuproine could enhance the amplitude of the contractions in the pregnant uterus. These effects were blocked by a purinergic receptor antagonist, suramin (100 μM) and did not occur following the administration of neocuproine–copper(I) complex or copper(II) chelator cuprizone. α,β-methylene ATP increased the amplitude and frequency of contractions in the pregnant uterus, but not affected the contractions in the ovariectomized non-pregnant rat uterus, and neocuproine potentiated this facilitation effect. However, the suppressive effect of neocuproine on the ovariectomized non-pregnant rat uterus increased in the presence of α,β-methylene ATP. β-adrenoceptor blocker, propranolol or nitric oxide synthase inhibitor, l-nitroarginine did not affect the responses to neocuproine. These findings suggest that neocuproine can affect the uterus contractile activity by modulation purinergic excitatory responses and that copper(I)-sensitive mechanisms may play a role in this effect.